Streptonigrin, a nonintercalative antitumor antibiotic, induced mammalian topoisomerase II dependent DNA cleavage in vitro. The cleavage activity of streptonigrin was comparable to that of demethylepipodophyllotoxin ethylidene-β-d-glucoside at a low concentration (≤10 µm) but one-third lower at a higher concentration (>250µm). Exposure of a reaction mixture containing streptonigrin, DNA, and topoisomerase II to an elevated temperature (65°C) resulted in substantial reduction in DNA cleavage, suggesting that the mechanism of the topoisomerase II dependent DNA cleavage induced by streptonigrin was through the formation of a cleavable complex previously reported for topoisomerase II poisons such as 4′-(9-acridinylamino) methanesulfon-m-anisidide and epipodophyllotoxins.

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